Niclosamide - encapsulated lipid nanoparticles for the reversal of pulmonary fibrosis
2024
Yan Yu | Hongyao Liu | Liping Yuan | Meng Pan | Zhongwu Bei | Tinghong Ye | Zhiyong Qian
Pulmonary fibrosis (PF) is a serious and progressive fibrotic interstitial lung disease that is possibly life-threatening and that is characterized by fibroblast accumulation and collagen deposition. Nintedanib and pirfenidone are currently the only two FDA-approved oral medicines for PF. Some drugs such as antihelminthic drug niclosamide (Ncl) have shown promising therapeutic potentials for PF treatment. Unfortunately, poor aqueous solubility problems obstruct clinical application of these drugs. Herein, we prepared Ncl-encapsulated lipid nanoparticles (Ncl-Lips) for pulmonary fibrosis therapy. A mouse model of pulmonary fibrosis induced by bleomycin (BLM) was generated to assess the effects of Ncl-Lips and the mechanisms of reversing fibrosis in vivo. Moreover, cell models treated with transforming growth factor β1 (TGFβ1) were used to investigate the mechanism through which Ncl-Lips inhibit fibrosis in vitro. These findings demonstrated that Ncl-Lips could alleviate fibrosis, consequently reversing the changes in the levels of the associated marker. Moreover, the results of the tissue distribution experiment showed that Ncl-Lips had aggregated in the lung. Additionally, Ncl-Lips improved the immune microenvironment in pulmonary fibrosis induced by BLM. Furthermore, Ncl-Lips suppressed the TGFβ1-induced activation of fibroblasts and epithelial−mesenchymal transition (EMT) in epithelial cells. Based on these results, we demonstrated that Ncl-Lips is an efficient strategy for reversing pulmonary fibrosis via drug-delivery.
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